We have shown that NA experience profound decrements in lung function and increased alveolar tissue inflammation. Thus, we investigated the changes in PAR at night in subjects with NA. Seven NA and 4 nonasthmatic controls (C) underwent two bronchoscopies in a random order at 4 pm and 4 am. The bronchoscope was wedged in the anterior segment followed by insertion of a size 5 French catheter. Warm, saturated air at flows ranging from 100 ml/min-1000 ml/min exited the catheter through one lumen and pressure was measured through the second lumen. Resistance (Rp) was defined as the pressure/flow averaged over two or more flow levels for each subject before and after 0.3 terbutaline (tb) SQ. Flow was stopped at functional residual capacity and the pressure was allowed to decay for 10 seconds; the final pressure was termed the closing pressure (Pc). The Rp in NA was significantly higher than C at 4 pm and 4 am: (4 pm: 0.011+/-0.001 (C) vs. 0.136+/-0.019 (NA) cm H20/ml/min, p=0.008; 4 am: 0.009+/-0.002 (C) vs. 0.150+/-0.04 (NA), p=0.001). Within the NA group, 2 distinct responses were observed despite similar % overnight falls in FEV1 (table). Group Rp (cm H20/ml/min) Pc(cm H20) %FEV1 % fall FEV1 (hs-4am) A - 4p 0.177+/-0.009 6.6+/-3.5 58.3+/-4.6 A - 4a 0.125+/-0.070 9.5+/-5.7 55.0+/-7.3 21.6+/-4.9 B - 4p 0.105+/-0.021 10.9+/-6.9* 71.5+/-8.9 B - 4a 0.168+/-0.040 26.8+/-8.1* 67.5+/-6.3 20.3+/-6.8 Group A exhibited an "airway" response with a lower, unchanging Pc, low FEV1 and a significant response to tb. Group B exhibited a "parenchymal" response with increased Pc at night consistent with loss of parallel conducting units in the small airways, a higher FEV1 and no significant response to tb (response to tb at 4 pm: delta Rp (pre-post tb): 0.164+/- 0.005 vs. -0.005+/-0.005 cm H20/ml/min in groups A and B, p=0.03). These different contributions to PAR may offer insight into the natural history and pathophysiology of asthma.